title: Photoexpulsion of surface-grafted ruthenium complexes and subsequent release of cytotoxic cargos to cancer cells from mesoporous silica nanoparticles.
abstract: Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions.
authors.affiliation: Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Frasconi
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Liu
authors.forename: Juying
authors.initials: J
authors.lastname: Lei
authors.forename: Yilei
authors.initials: Y
authors.lastname: Wu
authors.forename: Elena
authors.initials: E
authors.lastname: Strekalova
authors.forename: Dmitry
authors.initials: D
authors.lastname: Malin
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ambrogio
authors.forename: Xinqi
authors.initials: X
authors.lastname: Chen
authors.forename: Youssry Y
authors.initials: YY
authors.lastname: Botros
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Cryns
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Sauvage
authors.forename: J Fraser
authors.initials: JF
authors.lastname: Stoddart
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008027:Light; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C483523:ruthenium dipyridophenazine; D012822:Silicon Dioxide; D004247:DNA; D017239:Paclitaxel